tert-Butanol → (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol

A 1.0M t-BuOK solution in 2-methyl-2-propanol (0.220 mL, 0.220 mmol) was diluted into 2-propanol (12 mL). To the resulting solution was added RuCl(p-cymene)[(S,S)-Ts-DPEN] (28 mg, 0.044 mmol) and 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone (1.2 g, 4.4 mmol). The mixture was hydrogenated at 50° C. under 450 psig hydrogen gas for 16 h. Then, the mixture was evaporated. The residue was dissolved in CH2Cl2 (50 mL), and this solution was washed with 1N NaOH (2×50 mL), water (50 mL) and brine (50 mL). The organic phase was evaporated and the residue was loaded directly onto a silica gel column, using a hexanes-ethyl acetate gradient. The appropriate fractions were pooled and evaporated. The residue was slurried with MTBE (20 mL) for 1 h and filtered. The filter was washed with MTBE (5 mL) and the solids were dried under vacuum to afford (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol as a white solid (0.63 g, 52% yield); achiral HPLC (Hypersil BDS C8, 5.0 μm, 250×4.6 mm, 1.5 mL/min, 278 nm, 90/10 gradient to 80/20 0.1% aqueous TFA/MeOH over 10 min then gradient to 10/90 0.1% aqueous TFA/MeOH over the next 15 min): 11.38 (99.7%); chiral HPLC (Chiralpak AD-H 5.0 μm Daicel, 250×4.6 mm, 1.0 mL/min, 280 nm, 85:15 heptane-i-PrOH): 17.77 (9.1%), 20.14 (90.9%).

1. customThen, the mixture was evaporated
2. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
3. washthis solution was washed with 1N NaOH (2×50 mL), water (50 mL) and brine (50 mL)
4. customThe organic phase was evaporated
5. customevaporated
6. filtrationfiltered
7. washThe filter was washed with MTBE (5 mL)
8. customthe solids were dried under vacuum

ORD record

ord-4fa6f113f7744f388b486dbc12cb361f

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126906B2